Impacts of fungicide resistance and product loss

(Zymoseptoria tritici case study)

Neil Paveley, ADAS

Disease control sustainable if:

• Unlimited supply of new disease resistance genes and fungicide modes of action that are:

- accessible (financial & technical constraints)

- safe (regulatory & political constraints)

and

• Introduce new disease resistance genes and fungicide modes of action faster than pathogens defeat them

Broad-spectrum systemic modes of action:

• Azoles 1970s

• Strobilurins 1990s

• SDHIs (new generation) 2010s

• Next new mode of action ??

Regulatory uncertainty?

Years to First Detection of Resistance (n = 61) for single-site fungicides

0

1

2

3

4

5

6

7

8

9

10

1-2

3-4

5-6

7-8

9-10

11-1

2

13-1

4

15-1

6

17-1

8

19-2

0

21-2

2

23-2

4

25-2

6

27-2

8

FDR time (years)

Nu

mb

er

of

cases

Multi-site FDR times

>18 years

Grimmer et al., 2014. Pest Man. Sci.

Azole efficacy (full label dose)

Variance accounted for = 43.2%

0

10

20

30

40

50

60

70

80

90

100

1996 1999 2002 2005 2008 2011 2014

Septo

ria p

erc

ent

contr

ol

Proline

Opus / Ignite

Variance accounted for = 62.4%

0

10

20

30

40

50

60

70

80

90

100

1996 1999 2002 2005 2008 2011 2014

0

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0 1 2

DOSE

SE

PT

OR

IA T

RIT

ICI (%

)

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70

0 1 2

DOSE

0

10

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0 1 2

DOSE

2002 2003 2004

Pyraclostrobin (HGCA data)

QoI (strobilurin) efficacy

SDHI efficacy

Scalliet G, Bowler J, Luksch T, Kirchhofer-Allan L, Steinhauer D, et al. (2012) Mutagenesis and Functional Studies with Succinate Dehydrogenase Inhibitors in the Wheat Pathogen Mycosphaerella graminicola. PLoS ONE 7(4): e35429. doi:10.1371/journal.pone.0035429 http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0035429

What should we do?

Isolate CYP51 variant Epoxi Prochl Tebu Prot-des

Reference EC50 values in μg/ml n=4 Wild-type 0.0029 0.0164 0.072 0.0014 1994-2008 Resistance factor n=3 Y137F 2.8 0.9 1.2 0.6 n=2 Y137F & S524T 12 5.8 4.7 1.8 n=11 L50S, V136A & Y461H 55 25 4.8 8.8 n=35 L50S, I381V & Y461H 81 3.5 36 39 n=4 L50S, S188N, I381V, ∆ & N513K 86 3.2 28 15 n=47 L50S, S188N, A379G, I381V, ∆ & N513K 149 1.2 82 21 2009-2014

n=19 L50S, S188N, I381V, ∆ & N513K + CYP51 389 17 235 92 n=6 L50S, V136A, Y461S & S524T 206 62 5.4 46 n=2 V136C, I381V, Y461H & S524T 1111 15 110 93 n=1 L50S, D134G, V136A, Y461S & S524T 209 12 6.5 112 n=35 L50S, D134G, V136A, I381V & Y461H 196 11 5.0 102 n=7 L50S, V136A, I381V, Y461H & S524T 529 19 20 181 n=3 L50S, V136C, S188N, I381V, Y461H, S524T 733 7.9 69 85 n=1 L50S, S188N, A379G, I381V, ∆, N513K & S524T 477 4.5 77 81 n=1 L50S, S188N, H303Y, A379G, I381V, ∆ & N513K 376 2.3 62 109 n=6 L50S, D134G, V136A, I381V, Y461H & S524T 809 18 11 336 n=6 L50S, V136A, S188N, A379G, I381V, ∆ & S524T 999 12 21 418 n=4 L50S, V136C, S188N, A379G, I381V, ∆ & S524T 1486 3.3 242 162 n=4 L50S, V136A, S188N, A379G, I381V, ∆, N513K & S524T 923 7.7 22 623 n=1 L50S, S188N, I381V, ∆ & N513K + CYP51 + efflux 1428 66 303 207

Azole insensitive isolates (data courtesy Bart Fraaije, Rothamsted)

Low frequency of most ‘resistant’ isolates in field populations (fitness penalties?)

Van den Bosch et al. 2011 Plant Pathology 60, 597-606

First detection of resistance

Loss of effective control

Systems providing experimental evidence: Pathogen Crop Modes of action

Blumeria graminis f.sp. hordei Barley DMI, amines, QoI, pyrimidine

Zymoseptoria tritici Wheat DMI, QoI

Blumeria graminis f.sp. tritici Wheat DMI, amines

Venturia inequalis Apple DMI, MBC, QoI

Polyscytalum pustulans Potato MBC

Pythium aphanidermatum Ryegrass Phenylamide

Plasmopara viticola Grapevine QoI, phenylamide, cyanoacetamide

Botrytis cinerea Strawberry, grapevine, geranium Dicarboxamide, AP, hydroxyanilides

Podosphaera xanthii Cucurbit DMI, MBC

Phytophthora infestans Potato, tomato Phenylamide

Rhynchosporium secalis Barley DMI

Erwinia amylovora Pepper Glucopyranosyl antibiotic

Xanthomonas vesicatoria Pepper Glucopyranosyl antibiotic

Cercospora beticola Sugar beet MBC

Tapesia spp. Wheat MBC

Colletotrichum gleosporioides Euonymus MBC

Parastagonospora nodorum Wheat DMI, MBC

Pseudoperonospora cubensis Cucumber CAA

Helminthosprium solani Potato MBC

van den Bosch et al. 2014 Annual Review Phytopathology

Increase selection

No effect Decrease selection

Increase dose 16 1 2

Increase spray number 6 0 0

Split the dose 10 0 1

Add mixture partner 1 6 46

Alternate (replace sprays) 1 2 9

Adjust timing 3 1 2

van den Bosch et al. 2014 Governing principles can guide resistance management tactics Annual Review Phytopathology

Practical trade-offs: Reducing dose or limiting number of treatments reduces efficacy.

Limiting number of treatments constrains use of mixtures.

Need another effective MOA to mix or alternate with.

Knowledge gaps: Mixtures vs. alternation when there is concurrent selection for resistance against two MOA?

Which resistance management tactics work for monocyclic pathogens?

Septoria in treated crops

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4

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14

16

1 2 3 4 5

Sep

tori

a (%

)

Number of fungicide applications

Series3

Series1

2010 (3.1 treatments)

Leaf 1

Leaf 2

0

2

4

6

8

10

12

14

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Sep

tori

a le

af 2

(%

)

Yield response to fungicide treatment

(long-term RL rolling average)

Fungicide MOA + Fungicide MOA

Host resistance gene + Host resistance gene

Host resistance + Fungicide

+

‘Mixtures’ for effective control and slow pathogen evolution

What should we do?

• Resistance is not Schrodinger’s cat – it does not change when we observe it

- don’t change strategy on detection of resistance

• Argue for pesticide regulation based on risk not hazard

• Implement evidence-based resistance management

• Fill evidence gaps (monocyclic diseases, mixtures vs. alternation with concurrent selection)

• Forecast disease to minimise selection of resistant strains

• Integrate chemical and genetic control - more sustainable than either alone

• Enable high-yielding, disease resistant varieties

- RL criteria, tolerance, yield drag, durability